Medical endoprostheses or implants for a wide variety of applications are known in large numbers from the prior art. Implants in the sense of the present invention are understood to be endovascular prostheses or other endoprostheses, e.g., stents, fastening elements for bones, e.g., screws, plates or nails, surgical suture materials, intestinal clamps, vascular clips, prostheses in the area of hard and soft tissue as well as anchoring elements for electrodes, in particular pacemakers or defibrillators.
Stents are used as implants especially frequently today for treatment of stenoses (vascular occlusions). They have a body in the form of a tubular, possibly perforated, or hollow cylindrical basic mesh, which is open at both longitudinal ends. The tubular basic mesh of such an endoprosthesis is inserted into the blood vessel to be treated and serves to support the blood vessel. Stents have become established for treatment of vascular diseases in particular. Through the use of stents, constricted areas in the vessels can be dilated, resulting in a wider lumen. Although an optimum vascular cross section, which is needed primarily for successful treatment, can be achieved by using stents or other implants, the permanent presence of such a foreign body initiates a cascade of microbiological processes, leading to a gradual overgrowth of the stent and in the worst case to a vascular occlusion. One approach to solving this problem consists of manufacturing the stent and/or other implants from a biodegradable material.
The term “biodegradation” is understood to refer to hydrolytic, enzymatic and other metabolic degradation processes in a living organism, where these processes are caused mainly by the body fluids coming in contact with the biodegradable material of the implant and leading to a to gradual dissolution of the structures of the implant containing the biodegradable material. The implant loses its mechanical integrity at a certain point in time through this process. The term “biocorrosion” is often used as synonymous with the term “biodegradation.” The terms “bioresorption” and “bioabsorption” refer to the subsequent resorption or absorption of the degradation products by the living organism.
Materials suitable for implants that are biodegradable in the body may contain polymers or metals, for example. The implant body may be made of several of these materials. These materials have in common their biodegradability. Examples of suitable polymer compounds are the polymers from the group comprising cellulose, collagen, albumin, casein, polysaccharides (PSAC), polylactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D,L-lactide-co-glycolide (PDLLA-PGA), polyhydroxybutyric acid (PHB), polyhydroxyvaleric acid (PHV), polyalkyl carbonates, polyorthoesters, polyethylene terephtalate (PET), polymalonic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids and their copolymers as well as hyaluronic acid. Depending on the desired properties, the polymers may be present in pure form, in derivatized form, in the form of blends or as copolymers. Biodegradable metallic materials are based on alloys of magnesium and/or iron. The present invention preferably relates to implants whose biodegradable material contains at least partially a metal, preferably iron, manganese, zinc and/or tungsten, in particular an iron-based alloy (hereinafter simply “iron alloy”).
One goal in the implementation of biodegradable implants is to control degradability in accordance with the desired treatment and/or use of the respective implant (coronary, intracranial, renal, etc.). For many therapeutic applications, for example, an important target corridor is that the implant must lose its integrity after a period of four weeks to six months. The term “integrity.” i.e., mechanical integrity, is understood to refer to the property whereby the implant has hardly any mechanical losses in comparison with the undegraded implant. This means that the implant still has so much mechanical stability that the collapse pressure, for example, has declined only slightly, i.e., to 80% of the nominal value at most. The implant may thus retain its main function, namely keeping the blood vessel open, while retaining its integrity. Alternatively, integrity may be defined as meaning that the implant still has so much mechanical stability that it is hardly subject to any geometric changes in its stress state in the vessel; for example, it does not collapse to any significant extent, i.e., it still has 80% of the dilatation diameter under stress or, in the case of a stent, hardly any of the load-bearing struts are broken.
Implants with am iron alloy, in particular stents containing iron, are especially inexpensive and simple to manufacture. For treatment of stenoses, for example, these implants lose their mechanical integrity and/or supporting effect only after a comparatively long period of time, i.e., only after remaining in the treated body for approx. two years. This means that in this application, the collapse pressure of implants containing iron declines too slowly over a period of time.
Various mechanisms of controlling the degradation of magnesium implants have already been described in the prior art. For example, these are based on organic and inorganic protective layers or combinations thereof which present a resistance to the human corrosion medium and the corrosion processes taking place there. Approaches known in the past for solving this problem have been characterized in that barrier layer effects are achieved, based on a spatial separation, preferably free of defects, between the corrosion medium and the metallic material. These approaches result in a longer degradation time. Thus, the degradation protection is ensured by variously formulated protective layers and by defined geometric distances (diffusion barriers) between the corrosion medium and the degradable base material of the implant body (e.g., magnesium or Mg alloys). Other approaches are based on alloy components of the biodegradable material of the implant body, which influence the corrosion process by displacement of the position in the electrochemical voltage series. Other approaches in the field of controlled degradation induce intended breaking effects by applying physical changes (e.g., local changes in cross section) and/or chemical changes in the stent surface (e.g., multilayers with different chemical compositions locally). However, with the approaches mentioned so far, it is not usually possible to make the dissolution due to the degradation process and its resulting breakage of webs occur in the required time window. The result is that degradation of the implant begins either too early or too late or there is too much variability in the degradation.